Synthesis of low-hemolytic antimicrobial dehydropeptides based on gramicidin s.

abstract：:Reaction of 1-(S)-[3-hydroxy-2-(phosphonomethoxy)propyl]-5-azacytosine (1) with dicyclohexylcarbodiimide and N,N,-dicyclohexyl-4-morpholinocarboxamidine in dimethylformamide at elevated temperature afforded the corresponding cyclic phosphonate 2, that is, 1-{[(5S)-2-hydroxy-2-oxido-1,4,2-dioxaphosphinan-5-yl]methyl}-5...

journal_title：Journal of medicinal chemistry

authors： Krecmerová M,Holý A,Pohl R,Masojídková M,Andrei G,Naesens L,Neyts J,Balzarini J,De Clercq E,Snoeck R

更新日期：2007-11-15 00:00:00

abstract：:A series of [(heteroarylamino)phenyl]alkanoic acids having pyridine, quinoline, or pyrimidine as the heteroaryl moiety was prepared as potential antiinflammatory agents. Among them, 2-[4-(2-pyridylamino)phenyl]propionic acid (14b) showed excellent antiinflammatory and analgesic activities with less tendency to cause g...

journal_title：Journal of medicinal chemistry

authors： Hino K,Nakamura H,Nagai Y,Uno H,Nishimura H

更新日期：1983-02-01 00:00:00

abstract：:A series of S-alkylated derivatives of 5-mercapto-2'-deoxyuridine have been prepared by alkylation of the preformed nucleoside. Two of these compounds, the S-propargyl and S-allyl derivatives, have shown significant antiviral activity against Herpes simplex type 1 in HeLa TK- cells but appear to be less effective in t...

journal_title：Journal of medicinal chemistry

authors： Dinan FJ,Bardos TJ

更新日期：1980-05-01 00:00:00

abstract：:Ring-constrained adenosine analogues have been designed to act as dual agonists at tissue-protective A(1) and A(3) adenosine receptors (ARs). 9-Ribosides transformed into the ring-constrained (N)-methanocarba-2-chloro-5'-uronamides consistently lost affinity at A(1)/A(2A)ARs and gained at A(3)AR. Among 9-riboside deri...

journal_title：Journal of medicinal chemistry

authors： Jacobson KA,Gao ZG,Tchilibon S,Duong HT,Joshi BV,Sonin D,Liang BT

更新日期：2005-12-29 00:00:00

abstract：:A series of 7(8 leads to 11 alpha)abeo steroids was synthesized by a modification of the previously described total synthesis of this class of compounds and evaluated for biological activity. In general, there was a marked reduction in the relative binding affinities of these compounds for the rabbit uterus estrogen a...

journal_title：Journal of medicinal chemistry

authors： Wani MC,Rector DH,White DH,Pitt CG,Kimmel GL

更新日期：1977-04-01 00:00:00

abstract：:A series of structurally constrained derivatives of the potent H 3 inverse agonist 1 was designed, synthesized, and evaluated as histamine H 3 receptor inverse agonists. As a result, the N-cyclobutylpiperidin-4-yloxy group as in 2f was identified as an optimal surrogate structure for the flexible 1-pyrrolidinopropoxy ...

journal_title：Journal of medicinal chemistry

authors： Nagase T,Mizutani T,Sekino E,Ishikawa S,Ito S,Mitobe Y,Miyamoto Y,Yoshimoto R,Tanaka T,Ishihara A,Takenaga N,Tokita S,Sato N

更新日期：2008-11-13 00:00:00

abstract：:Several candidate retinoid antagonists were designed on the basis of the ligand superfamily concept and synthesized. Retinoidal activities of these benzimidazole and benzodiazepine derivatives were examined by assay of differentiation-inducing activity on human promyelocytic leukemia cell line HL-60. The parent benzim...

journal_title：Journal of medicinal chemistry

authors： Eyrolles L,Kagechika H,Kawachi E,Fukasawa H,Iijima T,Matsushima Y,Hashimoto Y,Shudo K

更新日期：1994-05-13 00:00:00

abstract：:Recent trends in drug discovery include methods to identify dual and triple activating drugs. This approach is being successfully employed in malaria, cancer, asthma, insulin resistance, etc. Molecular field analysis has been employed in correlating pharmacological data and field parameters. In this paper we introduce...

journal_title：Journal of medicinal chemistry

authors： Khanna S,Sobhia ME,Bharatam PV

更新日期：2005-04-21 00:00:00

abstract：:A series of thiazolothiazepines were prepared and tested against purified human immunodeficiency virus type-1 integrase (HIV-1 IN) and viral replication. Structure-activity studies reveal that the compounds possessing the pentatomic moiety SC(O)CNC(O) with two carbonyl groups are in general more potent against purifie...

journal_title：Journal of medicinal chemistry

authors： Neamati N,Turpin JA,Winslow HE,Christensen JL,Williamson K,Orr A,Rice WG,Pommier Y,Garofalo A,Brizzi A,Campiani G,Fiorini I,Nacci V

更新日期：1999-08-26 00:00:00

abstract：:The practices and tactics employed in successful optimizations are examined, judged from the trajectories of ligand efficiency and property evolution. A wide range of targets is analyzed, encompassing a variety of hit finding methods (HTS, fragments, encoded library technology) and types of molecules, including those ...

journal_title：Journal of medicinal chemistry

authors： Young RJ,Leeson PD

更新日期：2018-08-09 00:00:00

abstract：:A series of D-erythro- and L-threo-ceramide analogues was synthesized and investigated for their ability to reverse the inhibitory effects of fumonisin B(1) (FB(1)) on axonal growth in hippocampal neurons. The analogues contained either a C(7) side chain or a phenyl group substituted for the C(13) residue present in n...

journal_title：Journal of medicinal chemistry

authors： Van Overmeire I,Boldin SA,Dumont F,Van Calenbergh S,Slegers G,De Keukeleire D,Futerman AH,Herdewijn P

更新日期：1999-07-15 00:00:00

abstract：:Glycosylated β-endorphin analogues of various amphipathicity were studied in vitro and in vivo in mice. Opioid binding affinities of the O-linked glycopeptides (mono- or disaccharides) and unglycosylated peptide controls were measured in human receptors expressed in CHO cells. All were pan-agonists, binding to μ-, δ-,...

journal_title：Journal of medicinal chemistry

authors： Li Y,St Louis L,Knapp BI,Muthu D,Anglin B,Giuvelis D,Bidlack JM,Bilsky EJ,Polt R

更新日期：2014-03-27 00:00:00

abstract：:The homologous recombination (HR) pathway plays a crucial role in the repair of DNA double-strand breaks (DSBs) and interstrand cross-links (ICLs). RAD51, a key protein of HR, possesses a unique activity: DNA strand exchange between homologous DNA sequences. Recently, using a high-throughput screening (HTS), we identi...

journal_title：Journal of medicinal chemistry

authors： Huang F,Mazina OM,Zentner IJ,Cocklin S,Mazin AV

更新日期：2012-04-12 00:00:00

abstract：:Selectively substituted hydantoins 1 (15 examples), 4-hydroxy-2-imidazolidinones 2 (13 examples), 2-imidazolones 3 (10 examples), 2-imidazolidinones 4 (four examples), vicinal diamines 5 (two examples), and simple amino acid derivatives 6 (four examples) have been prepared and evaluated in the maximal electroshock sei...

journal_title：Journal of medicinal chemistry

authors： Cortes S,Liao ZK,Watson D,Kohn H

更新日期：1985-05-01 00:00:00

abstract：:A series of esters of 6beta-hydroxynortropane and the N-methyl analogue 6beta-tropanol were synthesized and screened versus binding of an antagonist (quinuclidinyl benzilate) and an agonist (oxotremorine-M) at sites on human m(1)-, m(2)-, m(3)-, and m(4)-muscarinic receptors in transfected cell membranes and on native...

journal_title：Journal of medicinal chemistry

authors： Daly JW,Gupta TH,Padgett WL,Pei XF

更新日期：2000-06-29 00:00:00

abstract：:Several 3-arylamino and 3-alkoxy-nor-beta-lapachone derivatives were synthesized in moderate to high yields and found to be highly potent against cancer cells SF295 (central nervous system), HCT8 (colon), MDA-MB435 (melanoma), and HL60 (leukemia), with IC(50) below 2 microM. The arylamino para-nitro and the 2,4-dimeth...

journal_title：Journal of medicinal chemistry

authors： da Silva EN Jr,de Deus CF,Cavalcanti BC,Pessoa C,Costa-Lotufo LV,Montenegro RC,de Moraes MO,Pinto Mdo C,de Simone CA,Ferreira VF,Goulart MO,Andrade CK,Pinto AV

更新日期：2010-01-14 00:00:00

abstract：:Cdc7 serine/threonine kinase is a key regulator of DNA synthesis in eukaryotic organisms. Cdc7 inhibition through siRNA or prototype small molecules causes p53 independent apoptosis in tumor cells while reversibly arresting cell cycle progression in primary fibroblasts. This implies that Cdc7 kinase could be considere...

journal_title：Journal of medicinal chemistry

authors： Menichincheri M,Albanese C,Alli C,Ballinari D,Bargiotti A,Caldarelli M,Ciavolella A,Cirla A,Colombo M,Colotta F,Croci V,D'Alessio R,D'Anello M,Ermoli A,Fiorentini F,Forte B,Galvani A,Giordano P,Isacchi A,Martina K,

更新日期：2010-10-28 00:00:00

abstract：:The directional properties of hydrogen bonds play a major role in determining the specificity of intermolecular interactions. An energy function which takes explicit account of these properties has been developed for use in the determination of energetically favorable ligand binding sites on molecules of known structu...

journal_title：Journal of medicinal chemistry

authors： Wade RC,Clark KJ,Goodford PJ

更新日期：1993-01-08 00:00:00

abstract：:Starting from a simple chalcone template, structure-activity relationship (SAR) studies led to a series of carboxylated, heteroaryl-substituted chalcone derivatives as novel, potent inhibitors of vascular cell adhesion molecule-1 (VCAM-1) expression. Correlations between lipophilicity determined by calculated logP val...

journal_title：Journal of medicinal chemistry

authors： Meng CQ,Ni L,Worsencroft KJ,Ye Z,Weingarten MD,Simpson JE,Skudlarek JW,Marino EM,Suen KL,Kunsch C,Souder A,Howard RB,Sundell CL,Wasserman MA,Sikorski JA

更新日期：2007-03-22 00:00:00

abstract：:A series of 6-benzoxazinylpyridazin-3-ones was prepared and evaluated for inhibition of cardiac phosphodiesterase (PDE) fraction III in vitro and for positive inotropic activity in vivo. 6-[3,4-Dihydro-3-oxo-1,4(2H)-benzoxazin-7-yl]-2,3,4,5-tetrahydro-5 - methylpyridazin-3-one (bemoradan) was found to be an extremely ...

journal_title：Journal of medicinal chemistry

authors： Combs DW,Rampulla MS,Bell SC,Klaubert DH,Tobia AJ,Falotico R,Haertlein B,Lakas-Weiss C,Moore JB

更新日期：1990-01-01 00:00:00

abstract：:Modification of the 2(S)-methylbutyryl moiety of mevinolin led to a series of side chain ester derivatives. A systematic exploration of the structure-activity relationships showed that the introduction of an additional aliphatic group on the carbon alpha to the carbonyl group increased potency. This observation led to...

journal_title：Journal of medicinal chemistry

authors： Hoffman WF,Alberts AW,Anderson PS,Chen JS,Smith RL,Willard AK

更新日期：1986-05-01 00:00:00

abstract：:A variety of N-(phenylsulfonyl)-N-phenylglycines 5, N-(phenylsulfonyl)-2-phenylglycines 6, and N-(phenylsulfonyl)anthranilic acids 7 were prepared as analogues of the N-(phenylsulfonyl)glycine 1 aldose reductase inhibitors. In the rat lens assay, several derivatives of 5 display greater inhibitory activity than the co...

journal_title：Journal of medicinal chemistry

authors： DeRuiter J,Borne RF,Mayfield CA

更新日期：1989-01-01 00:00:00

abstract：:The clinical use of anticancer lipids is severely limited by their ability to cause lysis of red blood cells prohibiting intravenous injection. Novel delivery systems are therefore required in order to develop anticancer ether lipids (AELs) into clinically useful anticancer drugs. In a recent article (J. Med. Chem. 20...

journal_title：Journal of medicinal chemistry

authors： Andresen TL,Jensen SS,Madsen R,Jørgensen K

更新日期：2005-11-17 00:00:00

abstract：:Glucose-dependent insulinotropic polypeptide (GIP) is a physiological insulin releasing peptide. We have developed two novel fatty acid derivatized GIP analogues, which bind to serum albumin and demonstrate enhanced duration of action in vivo. GIP(Lys(16)PAL) and GIP(Lys(37)PAL) were resistant to dipeptidyl peptidase ...

journal_title：Journal of medicinal chemistry

authors： Irwin N,O'Harte FP,Gault VA,Green BD,Greer B,Harriott P,Bailey CJ,Flatt PR

更新日期：2006-02-09 00:00:00

abstract：:A topological substructural approach to molecular design (TOSS-MODE) has been introduced for the selection and design of anticancer compounds. A quantitative model that discriminates anticancer compounds from the inactive ones in a training series was obtained. This model permits the correct classification of 91.43% o...

journal_title：Journal of medicinal chemistry

authors： Estrada E,Uriarte E,Montero A,Teijeira M,Santana L,De Clercq E

更新日期：2000-05-18 00:00:00

abstract：:Fragment-based drug design exploits initial screening of low molecular weight compounds and their concomitant affinity improvement. The multitude of possible chemical modifications highlights the necessity to obtain structural information about the binding mode of a fragment. Herein we describe a novel NMR methodology...

journal_title：Journal of medicinal chemistry

authors： Geist L,Mayer M,Cockcroft XL,Wolkerstorfer B,Kessler D,Engelhardt H,McConnell DB,Konrat R

更新日期：2017-11-09 00:00:00

abstract：:In previous reports illustrating the effects of conformational restriction of the N-terminal region of human pancreatic growth hormone releasing factor, we demonstrated that D-amino acid substitutions in either of positions 1, 2, or 3 resulted in greatly increased growth hormone releasing activity both in vivo and in ...

journal_title：Journal of medicinal chemistry

authors： Coy DH,Murphy WA,Sueiras-Diaz J,Coy EJ,Lance VA

更新日期：1985-02-01 00:00:00

abstract：:Twenty-two structural derivatives of clonidine [2-(2,6-dichlorophenylimino)imidazolidine] have been synthesized and their main physicochemical parameters (log P, deltaRM, pKa) determined. Quantitative correlations between the peripheral alpha-mimetic action (pithed rats) and physicochemical parameters pointed out the ...

journal_title：Journal of medicinal chemistry

authors： Rouot B,Leclerc G,Wermuth CG

更新日期：1976-08-01 00:00:00

abstract：:Syntheses of several tripeptide analogues of leupeptin containing C-terminal argininal, lysinal, or ornithinal units are presented. The synthetic analogues were tested as inhibitors of trypsin, plasmin, and kallikrein. (Benzyloxycarbonyl)-L-leucyl-L-leucyl-L-argininal (2a) was significantly less effective as an inhibi...

journal_title：Journal of medicinal chemistry

authors： McConnell RM,Barnes GE,Hoyng CF,Gunn JM

更新日期：1990-01-01 00:00:00

abstract：:Development of Grb2 Src homology 2 (SH2) domain binding inhibitors has important implications for treatment of a variety of diseases, including several cancers. In cellular studies, inhibitors of Grb2 SH2 domain binding have to date been large, highly charged peptides which relied on special transport devices for cell...

journal_title：Journal of medicinal chemistry

authors： Yao ZJ,King CR,Cao T,Kelley J,Milne GW,Voigt JH,Burke TR Jr

更新日期：1999-01-14 00:00:00